Automatic Stroke Screening on Mobile Application: Features of Gyroscope and Accelerometer for Arm Factor in FAST.

This study focuses on automatic stroke-screening of the arm factor in the FAST (Face, Arm, Speech, and Time) stroke screening method. The study provides a methodology to collect data on specific arm movements, using signals from the gyroscope and accelerometer in mobile devices. Fifty-two subjects were enrolled in this study (20 stroke patients and 32 healthy subjects). Given in the instructions of the application, the patients were asked to perform two arm movements, Curl Up and Raise Up. The two exercises were classified into three parts: curl part, raise part, and stable part. Stroke patients were expected to experience difficulty in performing both exercises efficiently on the same arm. We proposed 20 handcrafted features from these three parts. Our study achieved an average accuracy of 61.7%-74.2% and an average area under the ROC curve (AUC) of 66.2%-81.5% from the combination of both exercises. Compared to the FAST method used by examiners in a previous study (Kapes et al., 2014) that showed with an accuracy of 69%-77% for every age group, our study showed promising results for early stroke identification, giving that our study is based only on the arm factor.

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity.

OBJECTIVE: To define the lowest effective dose of botulinum toxin type A (Dysport) and safety in the treatment of adult patients with upper limb spasticity. DESIGN: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three does of Dysport (350, 500 100) U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS). RESULTS: fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500 U and the peak improvement was at week 8 after injection. A dose of 1000 U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication. CONCLUSION: This study suggest that treatment with Dysport reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500 U.

Pallister-Hall syndrome with hypoparathyroidism.

We report on a 5 2/12 year-old boy who presented with convulsions, precocious puberty due to a 1.9 x 1.9 x 1.6 hypothalamic hamartoma of the tuber cinereum, and some dysmorphic features including polysyndactyly of hands and feet, suggesting the diagnosis of Pallister-Hall syndrome. Hypocalcemia due to hypoparathyroidism was demonstrated, and this combination has not been reported previously. Therefore, we can add hypoparathyroidism as another feature of Pallister-Hall syndrome.

Isolated corpus callosal infarction secondary to pericallosal artery disease presenting as alien hand syndrome.

Two patients are described with the callosal type of alien hand syndrome. Both presented with abnormal feelings in the left upper limb and intermanual conflict without clinical evidence of callosal apraxia or frontal lobe dysfunction such as motor deficit or reflexive grasping. Imaging studies disclosed subacute infarction in the body and splenium of the corpus callosum due to pericallosal artery disease. These patients were unique in their presentation as a callosal type of alien hand syndrome secondary to ischaemic stroke.

Intracranial lymphoma: CT and MR findings.

The purposes of the present study were to describe CT and MR findings of intracranial lymphoma, to define imaging characteristics of primary and secondary intracranial lymphomas, and to compare CT and MR findings in the same patients. CT and MR studies of 26 patients with the diagnosis of intracranial lymphoma at King Chulalongkorn Memorial Hospital from 1988 to 2000 were reviewed. There were 22 cases of primary lymphoma (21 non-AIDS and 1 AIDS) and 4 cases of secondary lymphoma. Fifty-eight lesions were found. In primary lymphoma, most lesions were in the periventricular areas, appearing as multiple large well-defined margin masses with minimal surrounding edema and dense homogeneous enhancement on both CT and MR studies. The masses were hyperdense on CT scan, isointense on T1W images, and hyperintense to gray matter on T2W MR images. In one AIDS patient, rim enhancement of the lesion was found. Other uncommon findings included intratumoral hemorrhage, isolated mass in the brain stem and extracerebral locations. In secondary lymphoma, smaller and more lesions were noted. Diffuse ependymal enhancement was demonstrated in one case. The results suggest that MRI is more sensitive than CT scan in detecting intracranial lesions of lymphoma.

Thrombolytic treatment for acute ischemic stroke: a 2 year-experience at King Chulalongkorn Memorial Hospital.

We studied 9 stroke patients who received a thrombolytic agent at King Chulalongkorn Memorial Hospital. Six presented with stroke in the middle cerebral artery territory and three had basilar stroke. Seven patients were given intravenous thrombolysis and 2 received intra-arterial treatment. We strictly followed the inclusion and exclusion criteria for intravenous tissue plasminogen activator (rt-PA) according to the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA study. For patients receiving intraarterial thrombolysis, emergency angiograms were performed. Two patients with severe basilar stroke dramatically improved after intravenous thrombolysis and had very good outcome. Four patients with middle cerebral artery stroke became worse within 24 hours. Three of them died in the acute phase due to intracerebral hemorrhage (2 cases) and massive infarction with brain herniation (1 case). For intra-arterial treatment, good recanalization was seen but clinical improvement was insignificant. The result of thrombolytic treatment in this study was not so impressive, partly because we only treated the very severe cases. The efficacy of this treatment among our population needs to be further investigated.

Magnetic resonance spectroscopy of the brain in neurologically asymptomatic HIV-infected patients.

The CNS involvement is frequently found in human immunodeficiency virus (HIV) infection. The purpose of our study was to determine whether proton magnetic resonance spectroscopy (MRS) could detect early brain involvement in neurologically asymptomatic HIV-infected patients with normal MR imagings and to find the correlation between MRS and the immune status. We performed MRS in 30 HIV seropositive neurologically asymptomatic patients with normal MRI and compared the MRS findings with 13 controls. A statistically significant reduction in N-acetylaspartate (NAA)/creatine (Cr) and N-acetylaspartate (NAA)/choline (Cho) in both centrum semiovale (p < 0.005) and thalamic areas (p < 0.05) was found. There is no statistically significant difference as to choline (Cho)/creatine (Cr) and myoinositol (mI)/creatine (Cr) ratios in both regions. The difference of NAA/Cr was more pronounced in the white matter than in the gray matter. As for the immune status, there was a trend towards correlation between CD4 counts and NAA/Cr but devoid of statistical significance. Our results suggest that MRS is more sensitive than conventional MR imaging in detecting CNS involvement in neurologically asymptomatic HIV patients and may, therefore, be used for early detection of brain damage induced by HIV.

Comparison of transcranial Doppler ultrasound and computed tomography angiography in symptomatic middle cerebral artery stenosis.

Transcranial Doppler ultrasound (TCD) and computed tomography angiography (CTA) of 10 patients with middle cerebral artery territory stroke were studied. To obtain data from patients with presumed in situ middle cerebral artery (MCA) stenosis, the study excluded patients with a known source of cardiac emboli, significant carotid stenosis and classical lacunar syndrome. As the gold standard for this study, CTA demonstrated MCA stenosis in all patients (100%), while abnormal TCDs suggesting MCA stenoses were found in only six patients (60%). The stenotic sites differed among patients with normal and abnormal TCDs. Patients with false negative TCDs were found to have more distal lesions (distal M1 or M2 segment) whereas patients with TCD abnormalities tend to have more proximal lesions as demonstrated by CTA. It is concluded that an abnormal TCD is highly suggestive of stenosis of MCA. A normal TCD, however, does not exclude such a lesion, especially in patients with distal M1 or M2 stenoses. Therefore, TCD may not be the best screening test for intracranial vascular stenotic lesion in MCA territory stroke.

Multiple cranial neuropathy in Cogan's syndrome.

A 20 year old woman presented with recurrent alternative keratitis for four months. One month before admission, she developed progressive hearing loss, visual impairment, facial diparesis and bilateral trigeminal neuropathy. Cogan's syndrome was diagnosed. Prompt treatment with corticosteroid resulted in dramatic improvement of the ocular, otological and neurological dysfunctions.

Myelodysplastic syndromes in Thailand: a retrospective pathologic and clinical analysis of 117 cases.

To gain more insight into the understanding of myelodysplastic syndromes (MDS) as they occur in Thailand, a retrospective clinicopathologic analysis was conducted in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996 at the five major medical centers in various geographic regions of the country. The central reviewers independently examined the bone marrow and peripheral blood smears of all the patients and classify the disease according to the French-British-American (FAB) classification. There were a total of 117 eligible patients. The median age of the patients was 56 years (range 16-86). The male:female ratio was 1:1. Thirty-two percent of the patients were younger than 40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML, 9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of the patients. In the 34 patients in whom the cytogenetics in the bone marrow were analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were the most common aberration, each being detected in 26.7% of the patients. Transfusions were the main therapeutic modality in 80% of the patients. Kaplan-Meier analysis revealed a 5 year survival rate of 29% for the whole group with a median survival of 24 months. Twenty-five percent of the patients had progressed to acute myelogenous leukemia (AML) with a median time to disease-progression of 23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4, 19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression analysis revealed the percentage of blasts in the bone marrow as the only parameter significantly associated with survival and disease progression. On comparison with data from other countries, the age of Thai patients with MDS is considerably lower than the western population but is comparable to other asian countries. The distribution of the FAB subtypes and the survival of the patients are similar. The major prognostic features, however, lie in the percentage of blasts in the bone marrow rather than the degree of the observed cytopenia.

Takayasu arteritis: ultrasonographic evaluation of the cervico-cerebral arteries.

PURPOSE: To present the ultrasonographic findings of the cervico-cerebral arteries in patients with Takayasu arteritis. MATERIALS AND METHODS: We used duplex ultrasound to study the arteries in the neck including the common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA) and the vertebral arteries. For the intracranial arteries, transcranial Doppler ultrasound was used to study the blood flow velocities and directions in the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), ophthalmic artery, basilar and vertebral arteries. The ultrasonographic findings were compared with magnetic resonance angiography (MRA) and standard angiography. RESULTS: Four patients with the diagnosis of Takayasu arteritis were studied. One patient presented with ischemic optic neuropathy and was found to have absent radial pulse. Two patients presented with severe hypertension in young age. The other patient had accidental findings of unmeasurable blood pressure in both arms. One patient had abnormal carotid duplex ultrasound. He was found to have an occlusion of the right ICA. Thickening of the wall of the left ICA was also noted. Reduction of flow velocity in the MCA was demonstrated on TCD. There was evidence of collateral circulation from the contralateral carotid artery demonstrated by reversal of flow in the ipsilateral A1 segment of the ACA. MRA and angiography confirmed the ultrasound findings. Three patients had normal carotid duplex ultrasound but one of them was found to have a severe stenosis at the origin of the common carotid artery by MRA and angiogram. Absence of one vertebral artery was noted in three patients. MRA and angiogram confirmed the occlusion of the same vertebral arteries at their origins. In one patient, reversal of flow in the intracranial part (V4 segment) of the affected vertebral artery indicating collateral flow from contralateral vertebral and basilar arteries was demonstrated. CONCLUSION: Ultrasonography could be used as an additional noninvasive procedure apart from CT angiography, MRI and MRA in patients with Takayasu arteritis. Occlusion and wall thickening of the neck artery could be detected by color coded B-mode and Doppler ultrasound. Transcranial Doppler was useful in evaluation of flow velocity and flow direction of the arteries around the circle of Willis.

Transcranial Doppler ultrasound criteria for hemodynamically significant internal carotid artery stenosis based on residual lumen diameter calculated from en bloc endarterectomy specimens.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) is often used in conjunction with carotid duplex ultrasonography (CDUS) to evaluate the hemodynamic significance of internal carotid artery (ICA) stenosis. We examined the sensitivity and specificity of TCD criteria for detection of a hemodynamically significant stenosis (residual lumen diameter < 1.5 mm) at the origin of the ICA. METHODS: We selected patients who underwent carotid end-arterectomy (CEA) and had preoperative TCD data available. Eighty-one patients underwent transorbital evaluation, 49 of whom also had transtemporal TCD performed. The endarterectomy specimens were removed en bloc and sectioned, and the minimal residual lumen diameter calculated by computer analysis. RESULTS: For the transorbital approach, the strongest indicators of a residual lumen diameter < 1.5 mm were reversed flow in the ipsilateral ophthalmic artery and a > 50% peak systolic velocity difference between the carotid siphons (distal ICAs) in patients with unilateral ICA origin stenosis. They were 100% specific and 31% and 26% sensitive, respectively. For the transtemporal approach in patients with a unilateral stenosis, a > 35% difference in ipsilateral middle cerebral artery (MCA) peak systolic velocity relative to the contralateral MCA or a > 50% difference in contralateral anterior cerebral artery (ACA) peak systolic velocity relative to the ipsilateral ACA were 100% specific for identifying a residual lumen diameter of < 1.5 mm. Sensitivities were 32% and 43%, respectively. Irrespective of contralateral stenosis, a > 35% difference in ipsilateral MCA peak systolic velocity relative to the ipsilateral posterior cerebral artery had a 100% specificity and a 23% sensitivity for detecting a < 1.5 mm minimal residual lumen diameter. CONCLUSIONS: Although the TCD sensitivity for detecting a hemodynamically significant stenosis is relatively low, it can be highly specific (up to 100%). We conclude that TCD enhances the specificity of highly sensitive CDUS criteria for detecting a hemodynamically significant ICA stenosis.

Carotid Doppler ultrasound criteria for internal carotid artery stenosis based on residual lumen diameter calculated from en bloc carotid endarterectomy specimens.

BACKGROUND AND PURPOSE: Carotid duplex ultrasound is widely used to screen patients for carotid endarterectomy and if combined with MR angiography and transcranial Doppler may be an alternative to conventional angiography in the preoperative assessment. We have examined the correlation between Doppler velocities and the residual lumen diameters of internal carotid arteries from surgical pathological specimens to establish Doppler criteria for residual lumen diameter independent of percent stenosis. METHODS: Ninety-one patients who underwent 99 carotid endarterectomies for internal carotid artery stenosis within 6 months of their carotid duplex ultrasound evaluation were studied. The endarterectomy specimens were removed en bloc, and the minimal residual lumen diameter was calculated by computer analysis. The sensitivity and specificity of the Doppler criteria for determining high-grade stenosis were calculated and receiver-operator curves generated. RESULTS: Peak systolic velocity (PSV), end-diastolic velocity (EDV),and carotid index (peak internal carotid artery velocity/ common carotid artery velocity) correlated with the residual lumen diameter. PSV > 440 cm/s, EDV > 155 cm/s, or carotid index > 10 indicated a residual lumen diameter of < or = 1.5 mm (specificity of 100% and sensitivity of 58%, 63%, and 30%, respectively). When these criteria were combined, the sensitivity increased to 72%. A PSV > 200 cm/s combined with either an EDV > 140 cm/s or a carotid index > 4.5 has a sensitivity of 96% and a specificity of 61%. CONCLUSIONS: Doppler criteria can be both specific and sensitive for detecting a significant stenosis, defined as a < or = 1.5 mm residual lumen diameter. By adjustment of the velocity criteria, it can be 100% specific or a highly sensitive test (96%).

Non-Hodgkin's lymphomas in Thailand. A retrospective pathologic and clinical analysis of 1391 cases.

BACKGROUND: Geographic variations in the histopathologic pattern of non-Hodgkin's lymphoma (NHL) are well documented. Insight into this epidemiologic data might shed light on the underlying etiology. Currently, there is a paucity of information regarding the pattern of NHL occurring in Thailand and Southeast Asia. The current nationwide study was undertaken to obtain a clearer definition of the disease among Thais and to compare this information with data from other Asian and Western countries. METHODS: A retrospective analysis of histopathologic subtypes and clinical features was conducted in 1391 patients (age > or = 15 years) with NHL, who were treated at 6 major medical centers in 4 representative areas of Thailand. One hundred and thirty unselected cases were immunohistochemically studied. The reports from other countries used for comparison were identified through a computerized search on MEDLINE. RESULTS: Of the total cases studied, follicular lymphomas constituted 3.8% and diffuse lymphomas 91.4%. The frequency of low and intermediate grade (including large cell immunoblastic, using the Working Formulation) were 12.8% and 72.9%, respectively. The most common histologic subtype was the diffuse large cell and large cell immunoblastic entity, which constituted 39.9% of the cases studied. The rate of small lymphocytic and diffuse small cleaved subtypes were higher than in the United States. Of the 130 cases studied, T-cell lymphoma comprised 16.1%, which was much less than in Japan, China, or Taiwan. CONCLUSIONS: The histopathologic pattern of NHL in Thailand was characterized by the features noted for Asia, i.e., a low rate of the follicular entity and a preponderance of the diffuse aggressive subtypes. In addition, the frequency of the small lymphocytic and diffuse small cleaved subtypes were increased compared with the Western population and the rate of T-cell lymphoma appeared to be less than in Far East Asia.

Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging.

PURPOSE: To evaluate acute stroke with conventional, multisection diffusion-weighted (DW), and hemodynamically weighted (HW) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The three MR imaging techniques were performed in 11 patients within 10 hours of the onset of acute hemiparesis. The volume of DW and HW abnormalities were compared with infarct volumes depicted at initial and/or follow-up MR or computed tomography (CT). RESULTS: Findings at DW and HW imaging were abnormal in nine of the 11 patients, despite normal findings at initial CT and/or MR. In all nine patients, infarcts were depicted at follow-up CT or MR. The DW abnormality was generally smaller and the HW abnormality was generally larger than the infarct volume determined at subsequent imaging. In the two patients with normal findings at DW and HW imaging, symptoms resolved completely within 1-48 hours. CONCLUSION: Different aspects of hyperacute cerebral ischemia are depicted at DW and HW imaging before infarction is depicted at conventional MR or CT. These techniques may improve stroke diagnosis and may contribute to advances in treatment.

Takayasu arteritis in Thailand: clinical and imaging features.

PURPOSE: To present and evaluate the clinical and imaging features of patients with Takyasu arteritis in Thailand. MATERIALS AND METHODS: Clinical and angiographic findings were studied in 63 patients with Takayasu arteritis collected at Chulalongkorn Hospital Medical School, Bangkok. Imaging features including CT scan in 15 patients, magnetic resonance imaging in 14 patients and magnetic resonance angiography in ten patients were evaluated and compared to angiography. RESULTS: Among 63 patients there were 43 females and 20 males with the ratio female to male 2.15:1. The most common age groups were in the third and fourth decades of life. The most common clinical findings were hypertension and absence or weakness of pulses. Elevated erythrocyte sedimentation rate was found in 50%. For angiography, the most common vessel affected was the abdominal aorta (20%). The second and third most common sites were renal arteries (18.7%) and the subclavian arteries (14.3%). Coronary artery involvement was found in two out of eight patients. No pulmonary involvement was found in eight cases studied by pulmonary angiography. For classification of angiogram, the most common type of involvement (66.7%) was extensive involvement of the aorta and branches (type V of new classification established from International Conferences on Takayasu arteritis in Tokyo 1994). No patient was found to have only involvement of brachiocephalic branches or ascending aorta and brachiocephalic branches. CT scan showed calcification in the vessel walls (8/15 cases) which helped in diagnosis of the disease. Wall thickness, surrounding tissue, appearance of the vessel and intraluminal thrombus could be well seen. Magnetic resonance imaging added more detail in multiple planes and could demonstrate vascular flow. High detection rate of the lesions (94.8%) was found for the aorta. The study was less sensitive for smaller vessels. Magnetic resonance angiography showed better correlation of the findings of brachiocephalic arteries compared to angiography. Subclavian steal syndrome could be diagnosed. For renal arteries, MR angiography could correctly demonstrate occlusion of renal artery in six out of eight cases. In the other two cases only stenoses of the vessels were found on angiograms. One renal arterial stenosis on MR angiography was confirmed by angiography. CONCLUSION: Takayasu arteritis could be found in Thailand. Clinical features were almost the same as in reports from other countries. Various forms of arterial involvement were demonstrated by imaging modalities. Angiography remained the best method for detection and diagnosis of Takayasu arteritis in correlation with clinical and laboratory findings. Although CT scan, magnetic resonance imaging and magnetic resonance angiography were limited and less sensitive for detection of the lesions, they were useful as noninvasive modalities showing more details of intraluminal clot, vascular wall and surrounding tissue which could be correlated with pathological findings and pathogenesis of the disease. Our study suggests that MR imaging and MR angiography can be screening and diagnostic techniques for patients with suspected Takayasu arteritis.

Primary meningioma intimately related to skull: case report and review of the literature.

A report is made of a primary meningioma intimately associated with the left sphenoid ridge and temporal bone of a 41-year-old woman. The lesion produced hyperostosis of the involved bones, ipsilateral proptosis, and reduced vision for 4.5 years. The radiotherapy yielded little improvement of the exophthalmos and vision. Review of 125 reported meningiomas intimately related to the skull and presenting primarily with hyperostosis and minimal soft tissue component, including the current case, disclosed that all but one affected the cranium proper, particularly the middle ear, temporal bone, frontal bone, and parietal bone. The exceptional one was in the mandible. They tended to occur between the fifth and seventh decades of life with the peak occurrence between the fifth and sixth decades. The average age was 46 years for overall. The female-to-male ratio was 2:1. Six of 125 primary meningiomas closely associated with the skull were malignant and two of these spread to the lungs. The pulmonary metastasis was spontaneous in one case.

Headache in brain tumor: a cross-sectional study.

Headache is one of the cardinal features of intracranial neoplasm. However, there is little published information on the prevalence and clinical profiles of headache in patients with brain tumor. This cross-sectional study recruited 171 cases of brain tumor. The average age was 39 years (range from 4 to 75 years). The female to male ratio was 1.2:1. The prevalence of headache was 71%. The duration of headache ranged from 3 days to 10 years with an average of 15.7 months. Most prominent headache profiles in this series were intermittent, nocturnal and early morning headache as well as headache upon arising. Most of the patients had mild to moderately severe headache. Headache is more common with tumors below the tentorium cerebelli. It is more prevalent in primary and intracerebral tumor than in metastatic and extracerebral tumor. Headache has lateralizing value, especially in patients with supratentorial lesions who have no obvious increased intracranial pressure.

Case report: chronic spinal cord compression from extramedullary haematopoiesis in thalassaemia--MRI findings.

A 27-year-old-man with beta-thalassaemia/HbE presented with signs and symptoms of spinal cord compression due to epidural extramedullary haematopoiesis. Magnetic resonance images demonstrated spinal cord constriction and atrophy suggesting that the disease process was long-standing. On transverse T2-weighted images, high signal intensity was observed within the spinal cord suggestive of post-compressive spinal cord myelomalacia or gliosis.

Cerebral abscesses due to Pseudomonas pseudomallei.

Two cases of cerebral abscesses caused by Pseudomonas pseudomallei are reported. The first case, a 51-year-old women had a sudden onset of progressive right hemiparesis and right facial palsy and died within 7 days. Postmortem examination disclosed brain abscess in association with disseminated infection outside the central nervous system. The second case, a 9-year-old boy displayed cerebral abscesses as an isolated manifestation. Recovery occurred after treatment with ceftazidime. Review of the ten case reports of cerebral melioidosis revealed that the lesion occurred in patients of all ages and was more common in men than in women. The frontoparietal lobe was the most common location. Fever, headache, and hemiparesis were frequent clinical manifestations while seizures, ataxia were uncommon. CT scanning, serum antibody titer along with hemoculture were useful investigate tools. The importance of early diagnosis and prompt treatment is emphasized for this fatal but treatable disease.